We have developed a clinically useful method (the laser Doppler instrument and its theory of operation) for clinical measurements of microcirculatory blood flow, the density of flowing red blood cells (RBCs), and mean RBC velocity. We have helped to commercialize this methodology and its application to clinical research. Our clinical studies have been directed toward examining normal and abnormal microvascular dynamics through noninvasive clinical studies of skin and nasal mucosa, and toward intraoperative clinical studies of muscle and of the CNS. Considerable theoretical work has been directed toward finding an adequate construct with which to interpret the physical measurements, and toward refining the accuracy of the microcirculatory measurements. We have discovered abnormal microcirculatory patterns and responses in the skin of patients with sickle-cell disease, hypertension, certain cardiac circulatory syndromes, diabetes, and skin cancer. We monitor the microcirculatory effects of therapy using this technique, thus affording a better understanding of the microcirculatory components of these diseases. A clinical protocol is in progress to determine if LDF measurements that show increases in skin blood flow as a function of cumulative radiation dose to the skin during therapy for certain deeper tumors may be predictive of the general tumor and tissue radiation sensitivity of a given patient. We are also studying the physics of motion artifacts, in particular those induced by scanning LDF used to provide 2-D maps of blood flow.